[Risk factor assessment and adverse outcome prediction of placenta accreta in pregnant women after cesarean section complicated with placenta previa: a national multicenter retrospective study].

Objective: To study the risk factors of adverse pregnancy outcomes for the diagnosis and treatment of pregnancy after cesarean section complicated with placenta previa. Methods: A national multicenter retrospective study was conducted to select a total of 747 pregnant women with the third trimester singleton pregnancy after cesarean section complicated with placenta previa from 12 tertiary hospitals in January 1st to December 31st, 2018. The risk factors of severe adverse outcomes [hysterectomy, intraoperative blood loss ≥1 000 ml, intraoperative diagnosis of placenta accreta spectrum disorders (PAS)] in pregnant women with second pregnancy complicated with placenta previa after cesarean section were investigated by logistic regression analysis. The roles of prenatal ultrasonography and magnetic resonance imaging (MRI) in the prediction of PAS and severe adverse outcomes were observed. According to whether vascular intervention was performed (uterine artery embolization or abdominal aortic balloon occlusion), the pregnant women were divided into the blocked group and the unblocked group, and the maternal and infant perinatal outcomes between the two groups were compared. Results: (1) General information: the hysterectomy rate of 747 pregnant women with second pregnancy complicated with placenta previa after cesarean section was 10.4% (78/747), the intraoperative blood loss ≥1 000 ml in 55.8% (417/747), and PAS was confirmed in 47.5% (355/747). The incidence of uterine rupture was 0.8% (6/747). (2) Analysis of risk factors for severe adverse outcomes: based on binary unconditioned logistic regression univariate and multivariate analysis, the risk factors for hysterectomy were the mode of vascular embolization and intraoperative blood loss. The probability of hysterectomy with uterine artery embolization was 5.319 times higher than that with abdominal aortic balloon occlusion (95%CI: 1.346-21.018). The risk factors of intraoperative blood loss ≥1 000 ml were the number of cesarean section delivery, ultrasonography indicated PAS and suspected PAS, intraoperative PAS and complete placenta previa. The risk factors for intraoperative PAS were uterine scar thickness, ultrasonography indicated PAS and suspected PAS, MRI indicated PAS and suspected PAS, and complete placenta previa. (3) The roles of ultrasonography and MRI in predicting PAS: the sensitivity and specificity of ultrasonography in predicting PAS were 47.5% and 88.4%; the kappa value was 0.279 (P<0.001), with fair agreement. The sensitivity and specificity of MRI to predict PAS were 79.2% and 97.8%, respectively. The kappa value was 0.702 (P<0.001), indicating a good agreement. The intraoperative blood loss and hysterectomy rate of pregnant women with PAS indicated by ultrasonography and MRI were significantly higher than those with PAS only by ultrasonography or MRI. (4) Influence of vascular occlusion on pregnancy outcome: there were no significant differences in intraoperative blood loss and incidence of intraoperative bleeding ≥1 000 ml between the blocked group and the unblocked group (all P>0.05). There was no significant difference in intraoperative blood loss between the pregnant women with abdominal aortic balloon occlusion, uterine artery embolization and those without occlusion (P=0.409). The hysterectomy rate of pregnant women with uterine artery embolization was significantly higher than those with abdominal aortic balloon occlusion [39.3% (22/56) vs 10.0% (5/50), P=0.001]. Conclusions: In the third trimester of pregnancy with placenta previa after cesarean section, MRI examination has better consistency in predicting PAS than ultrasonography examination. Ultrasonography examination combined with MRI examination could effectively predict the hysterectomy rate and intraoperative blood loss. Vascular occlusion could not reduce the amount of intraoperative blood loss. The hysterectomy rate of pregnant women with uterine artery embolization is higher than those with abdominal aortic balloon occlusion.

[The common morphology and clinical significance of the axillary arch].

Axillary arch is the most common type of axillary muscle fiber variation, with about 10.8% incidence in the Chinese population. Its natural forms are varied and fluid, with different starting points and terminations, and clinicians frequently lack recognition. Under commonly applicated sentinel lymph node biopsy, the axillary arch has been endowed with more clinical significance. The fabric of axillary arch will not only block lymphatic drainage in axilla and unclear anatomical level of axillary dissection, but also compress the axillary neurovascular bundle, causing upper limb venous thrombosis, lymphedema and nerve entrapment. The intumescent axillary arch may also show abnormal axillary bulge. In addition to finding axillary arch during cadaveric study and operation, several of imaging methods availably diagnose axillary arch preoperative, which can create new way for detection of axillary arch and extension of the surgical plan of sentinel lymph node biopsy. Although embryology and comparative anatomy have been used to explain the origin of the axillary arch, most of the ideas are still hypotheses and need further study.

[Pneumatosis cystoides intestinalis in lung transplant recipients: three cases report and literature review].

Objective: To report the clinical characteristics and treatment courses of pneumatosis cystoides intestinalis(PCI) after lung transplantation(LT). Methods: We included all cases of PCI after LT from March 2017 to June 2021 in China-Japan Friendship Hospital. In addition to our cases, we searched literatures published in Chinese and English languages using China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed/MEDLINE with the search terms"pneumatosis intestinalis"and"lung transplantation". The clinical characteristics and treatment courses of all cases were summarized and analyzed. Results: Three cases of PCI occurred after LT in this study, with an incidence of 0.804% (3/373). Thirteen related literatures were retrieved, with 51 cases enrolled. The median age of the 54 patients was 55.4 years (22-79 years), with 33 males and 21 females. 64.81% (35/54) of the 54 patients underwent LT for interstitial lung disease and 90.74% (49/54) underwent bilateral LT. Twenty-two cases(40.7%) were asymptomatic when PCI occurred. Thirty-eight cases (38/54,70.37%)had involvement of ascending colon, and 35 cases(35/54,64.81%)had involvement of transverse colon. Forty-three cases(43/54, 79.63%) were treated conservatively. The average interval between transplantation and PCI was 210 (5-2 495) days. Conclusion: PCI is a rare complication after lung transplantation, most often occurring in the colon. Most patients were asymptomatic and could improve by conservative treatments.

Examining the association between serum free fatty acids and blood levels of testosterone.

BACKGROUND: Multiple studies have uncovered the effects that ingested fat has on human blood levels of testosterone. Yet, few reports have discussed the effect of circulating serum free fatty acids (FFAs). The present study aimed to explore the relationship between serum free fatty acids and blood levels of testosterone. METHODS: In total, 5719 adults were pooled from the database of the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2012. Based on multivariable-linear regression models, we employed a total of 30 FFAs to interpret the relationship of FFAs with blood levels of testosterone. Two models with covariate adjustments were designated for further evaluation and analysis. RESULTS: Capric acid [ß = -0.014, 95% confidence interval (CI) = -0.023, -0.004, P = 0.005], myristic acid (ß = -0.001, 95% CI = -0.001, 0.000, P ≤ 0.001), pentadecanoic acid (ß = -0.013, 95% CI = -0.018, -0.008, P ≤ 0.001), margaric acid (ß = -0.011, 95% CI = -0.017, -0.005, P ≤ 0.001) and alpha-linolenic acid (ß = -0.001, 95% CI = -0.002, 0.000, P = 0.004) in the fully adjusted model were significantly negatively correlated with the testosterone level inh obese men. In the fully adjusted model for the female analysis, myristic acid, pentadecanoic acid, palmitic acid, margaric acid, stearic acid, myristoleic acid, oleic acid, nervonic acid and alpha-linolenic acid were found significantly associated with the testosterone level. CONCLUSIONS: Our findings indicate a significant negative correlation between serum FFAs and blood levels of testosterone. Furthermore, we reveal the essentiality of serum FFAs and their potential effects on the reduction of testosterone levels.

[Evaluation of the diagnosis and treatment of cesarean scar pregnancy induced in the second trimester: a national multicenter retrospective study].

Objective: To study the risk factors of adverse pregnancy outcomes for induced abortion of cesarean scar pregnancy in midtrimester. Methods: A national multicenter retrospective study was conducted. A total of 154 singletons pregnant women with cesarean scar pregnancy during the second trimester induced abortion by various reasons in 12 tertiary A hospitals were selected, their pregnant outcomes were observed and the risk factors of serious adverse outcomes were analyzed with univariate and multivariate logstic regression; the role of ultrasound and MRI in predicting placenta accreta and severe adverse outcomes was evaluated, the effectiveness of uterine artery embolization (UAE) in preventing hemorrhage in pregnant women with and without placenta accreta was compared. Results: Among 154 subjects, the rate of placenta accreta was 42.2% (65/154), the rate of postpartum hemorrhage≥1 000 ml was 39.0% (60/154), the rate of hysterectomy was 14.9% (23/154), the rate of uterine rupture was 0.6% (1/154). The risk factor of postpartum hemorrhage≥1 000 ml and hysterectomy was placenta accreta (P<0.01). For each increase in the number of parity, the risk of placenta accreta increased 2.385 times (95%CI: 1.046-5.439; P=0.039); and the risk of placenta accreta decreased with increasing ultrasound measurement of scar myometrium thickness (OR=0.033, 95%CI: 0.001-0.762; P=0.033). The amount of postpartum hemorrhage and hysterectomy rate in the group with placenta accreta diagnosed by ultrasound combined with MRI were not significantly different from those in the group with placenta accreta diagnosed by ultrasound only or MRI only (all P>0.05). For pregnant women with placenta accreta, there were no significant difference in the amount of bleeding and hysterectomy rate between the UAE group [median: 1 300 ml; 34% (16/47)] and the non-embolization group (all P>0.05); in pregnant women without placenta accreta, the amount of bleeding in the UAE group was lower than that in the non-embolization group (median: 100 vs 600 ml; P<0.01), but there was no significant difference in hysterectomy rate [2% (1/56) vs 9% (3/33); P>0.05]. Conclusions: (1) Placenta accreta is the only risk factor of postpartum hemorrhage≥1 000 ml with hysterectomy for induced abortion of cesarean scar pregnancy in midtrimester; multi-parity and ultrasound measurement of scar myometrium thickness are risk factors for placenta accreta. (2) The technique of using ultrasound and MRI in predicting placenta accreta of cesarean scar pregnancy needs to be improved. (3) It is necessary to discuss of UAE in preventing postpartum hemorrhage for induced abortion of cesarean scar pregnancy in midtrimester.

[Clinical analysis of 33 cases of chronic liver diseases overlapping with CMV infection].

Objective: To understand the clinical features and outcomes of chronic liver diseases overlapping with CMV infection. Methods: Clinical characteristics, treatment and outcome of patients of chronic liver diseases overlapping with CMV infection were analyzed retrospectively. T-test was used for measurement data and χ (2) test was used for count data. All measurement data were expressed by (x ± s). P > 0.05 was not determined as significant. P < 0.05 was regarded as statistically significant. Results: Chronic liver diseases overlapping with CMV infections had similar clinical features. Etiopathogenic treatment + symptomatic supportive treatment + CMV overlapping infection treatment (including antiviral therapy, corticosteroids consideration, clearing heat and traditional Chinese choleretic medicine, etc) were the primary principles of therapy. The incidence of cytomegalovirus infection accounted for 4.125% during the corresponding hospitalization period. Cytomegalovirus infection had relatively caused liver function damage in patients with milder clinical symptoms and signs. Biochemical indicators before and after treatment showed that there was no significant difference in total bilirubin (TBil) before (262.93 ± 178.944) µmol/L and after one week of treatment (245.08 ± 179.332) µmol/L (P > 0.05). However, when TBIL was compared with three (156.58 ± 147.461) µmol/L and four weeks (103.39 ± 102.218) µmol/L) of treatment, the decrease was significant (P < 0.05, P < 0.01). Alanine aminotransferase (ALT) after one week (293.57 ± 467.438) U/L (P < 0.01) of treatment was significantly lower than before treatment (782.34 ± 828.801) U/L. Gamma-glutamyl transferase (GGT) after treatment (202.52 ± 155.174)U/L was significantly lower than before treatment(280.69 ± 205.619)U/L). Total bile acid (TBA) was increased after treatment (198.04 ± 155.174)µmol/L, when compared with that of before treatment (62.93 ± 178.944)µmol/L. Biochemical indicators of liver diseases had shown typical features of cholestasis, and the slow and reduced flow of bile acid was tracked and observed. Compared with the advanced group (182.45 ± 214.169) umol/L, the total bilirubin in inflammation group (50.36 ± 26.282) umol/L was decreased (P < 0.05). Moreover, advanced group (122.18 ± 106.780) umol/L (P < 0.05) had elevated total bile acid normalization rate than that of bile acid group (54.82 ± 56.123) umol/L, and the inflammatory phase had significantly better outcome than those with advanced-stage. Conclusion: Chronic liver diseases overlapping with cytomegalovirus infection has a good therapeutic outcome in the inflammatory phase, but in the advanced-stage; the therapeutic efficacy and outcome is poor and perilous.

[Association between the time of neutrophils to the lowest and prognosis of patients with esophageal squamous cell carcinoma treated with non-operative therapy].

Objective: To investigate the association between the time of neutrophils to the lowest and prognosis of patients with esophageal squamous cell carcinoma (ESCC) treated with non-operative therapy. Methods: The clinical data of 325 non-operative treated ESCC patients were collected in this study. The X-title software was applied to establish optimal threshold of neutrophil reduction to the lowest value. According to the optimal threshold, the patients were divided into early group (115 cases) and late group (210 cases). The clinical features and survival time of the two groups were compared, and the factors of prognosis were analyzed by Cox regression model with univariate and multivariate analysis. Results: The X-title software demonstrated the optimal cutoff values for the time of neutrophils to the lowest was 39 days. The median overall survival time was 21.0 months in the early group which was significantly higher than that in the late group (16.0 months). Multivariate Cox regression analysis showed that the treatment methods and the time of neutrophils to the lowest were independent factors for overall survival of patients with ESCC treated by non-surgical therapy. Compared with radiotherapy alone, concurrent chemoradiation could benefit the survival (HR=0.64, P=0.026). The prognosis of patients in the late group of neutrophils to the lowest (HR=1.38, P=0.038) was poor compared with the early group. Furthermore, stratified by treatment methods, the overall survival of two groups showed statistically significant difference only in patients received concurrent chemoradiation. The mortality risk in the late group was higher than that in the early group (HR=3.53, P=0.010). Conclusion: The time of neutrophils to the lowest is an independent prognosis factor for non-operative treated ESCC patients. The prognosis of patients in the early group is better than that in the late group.

[Altered serum cytokine expression profile in systemic sclerosis and its regulatory mechanisms].

OBJECTIVE: To analyze the expression profile of serum cytokines in patients with systemic sclerosis (SSc) and explore its possible regulatory mechanisms. METHODS: Serum and DNA of peripheral blood mononuclear cells were collected from 30 SSc patients and 80 normal controls (NCs). According to the presence or absence of interstitial lung disease (ILD) in SSc, the patients were divided into SSc with ILD group and SSc without ILD group. According to the degree of skin involvement, the patients were divided into diffuse systemic scleroderma (dcSSc) group and limited systemic scleroderma (lcSSc) group. According to the presence of anti-topoisomerase-1 antibody (anti-Scl-70 antibody) in the serum of patients with SSc, they were divided into SSc Scl-70 (+) group and SSc Scl-70 (-) group. 27 cytokines in serum were detected by Luminex MAGPIX detection system and Bio-Plex Pro Human Cytokine 27-plex Assay kit: interleukin-1ß (IL-1ß), interleukin-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12P70, IL-13, IL-15, IL-17, basic fiber growth factor (BASIC FGF), eotaxin, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), interferon-gamma induced protein 10(IP-10), monocyte chemotactic protein 1(MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein 1ß(MIP-1ß), platelet-derived growth factor BB (PDGF-BB), regulated on activation in normal T-cell expressed and secreted (RANTES), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor(VEGF). Methylation sites were detected by Illumina 450K methylation chip. RESULTS: Compared with NCs group, the expression of 12 cytokines (BASIC FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IL-1ß, IL-1ra, IL-6, IP-10, MCP-1, TNF-α and RANTES) in the SSc group significantly increased (P<0.05), IL-5 was decreased expression in the SSc group (P<0.05), there was no significant difference in the expressions of the other 14 cytokines. Compared with lcSSc group, 9 cytokines (eotaxin, IL-5, MCP-1, IL-2, RANTES, IL17A, IL-8, MIP-1ß and PDGF-BB) increased in dcSSc group, but there was no significant difference. Compared with SSc without ILD group, IL-15 increased in SSC with ILD group [18.2 (172.97) ng/L vs. 2.03(0.05) ng/L, P<0.05]. Compared with SSc Scl-70 (-) group, the expression of IP-10 decreased in SSc Scl-70 (+) group [1 030 (2 196.6) ng/L vs. 1 878 (2 964) ng/L, P<0.05]. The correlation analysis of serum cytokines with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) showed that IL-6 was positively correlated with ESR (r =0.04, P= 0.017), MCP-1 (r=0.49, P=0.043) and MIP-1ß (r=0.41, P=0.007) positively correlated with CRP. By analyzing the changes of methylation sites of cytokines, it was found that cg17744604 in IL-10 TSS1500 region, cg06111286 in IL-12P70 TSS200 region, cg07935264 in IL-1ß TSS200 region, cg01467417 in IL-1ra TSS1500 region, cg03989987 in IL-1ra 5'UTR region and cg21099624 in VEGF TSS200 region were all hypomethylated. CONCLUSION: There were different cytokines expression profiles in the serum of SSc patients, and the altered cytokines were correlected with the degree of skin damage and pulmonary fibrosis. Many cytokines were regulated by methylation.

[Evaluation of the right ventricular function in patients with pneumoconiosis by echocardiography].

Objective: To investigate right ventricular function in patients with pneumoconiosis, and to provide a basis for quantitative diagnosis and treatment of pneumoconiosis in clinical practice. Methods: A total of 43 patients with pneumoconiosis who were hospitalized consecutively in Shijiazhuang Prevention and Treatment Center for Occupational Diseases from May 2015 to May 2016 were enrolled, and according to the stage of pneumoconiosis, they were divided into stage I group with 16 patients, stage II group with 14 patients, and stage III group with 13 patients. A total of 16 healthy subjects were enrolled as control group. Echocardiography was performed and the relevant parameters were recorded, i.e., right ventricular transverse diameter (RVTD), tricuspid annular plane systolic excursion (TAPSE), and right ventricular myocardial performance index(Tei index). Results: There were significant differences in Tei index and TAPSE between all groups (P <0.05) except between the stage I group and the control group in terms of Tei index (P>0.05) and between the stage I group and the stage II group in terms of TAPSE (P>0.05). Right ventricular Tei index was negatively correlated with TAPSE (r=-0.547,P<0.05). Conclusion: A combination of right ventricular Tei index and TAPSE can be used for early quantitative evaluation of right ventricular function in patients with pneumoconiosis.

Landing strategies focusing on the control of tibial rotation in the initial contact period of one-leg forward hops.

Anterior cruciate ligament (ACL) reconstruction (ACLR) surgeries successfully restore anterior tibial translation but not tibial rotation. This study aimed to explore landing strategies focusing on the control of tibial rotation at landing when the ACL is most vulnerable. Three groups of male subjects (50 ACLRs, 26 basketball players, and 31 controls) participated in one-leg forward hop tests for determining the tibial rotatory landing strategies adopted during the initial landing phase. The differences in knee kinematics and muscle activities between internal and external tibial rotatory (ITR, ETR) landing strategies were examined. A higher proportion of basketball players (34.6%) were found to adopt ITR strategies (controls: 6.5%), exhibiting significantly greater hopping distance and knee strength. After adjusting for hopping distance, subjects adopting ITR strategies were found to hop faster with straighter knees at foot contact and with greater ITR and less knee adduction angular displacement during the initial landing phase. However, significantly greater angular displacement in knee flexion, greater medial hamstring activities, and greater co-contraction index of hamstrings and medial knee muscles were also found during initial landing. Our results support the importance of the recruitments of medial hamstrings or the local co-contraction in assisting the rotatory control of the knee during initial landing for avoiding ACL injuries.

[Expression of peroxisome proliferator-activated receptors, fatty acid binding protein-4 in placenta and their correlations with the prognosis of pre-eclampsia].

Objective: To examine the mRNA and protein expression of peroxisome proliferator-activated receptors (PPAR) and fatty acid binding protein-4 (FABP-4) in placenta, and to investigate their correlation with the prognosis of pre-eclampsia. Methods: The data of 177 women who delivered from January 2013 to December 2015 in Chinese People's Liberation Army No.94 Hospital were collected. Among them, 60 cases were term pregnancy and not in labor (TN); 46 cases were term pregnancy with preeclampsia and not in labor (TPE); 42 cases were preterm pregnancy and not in labor (PN); 29 cases were preterm pregnancy with pre-eclampsia and not in labor (PPE). Real-time PCR and western blot were used to examine the PPAR and FABP-4 mRNA expression and protein expression in placentas. And linear correlation was used to analyze the relationship between PPAR and FABP-4 protein expression and the prognosis of pre-eclampsia. Results: (1) Real-time PCR showed that: ① PPAR-α, PPAR-ß mRNA expression were not statistically different between placentas from TN and TPE (P>0.05), but PPAR-γ mRNA level in TPE (0.59±0.17) was significantly lower than that in TN (0.81±0.19, P<0.01). However, FABP-4 mRNA level in TPE (0.70±0.23) was significantly higher than that in TN (0.43±0.18, P<0.01). ②There were no statistical differences in PPAR-α, PPAR-ß mRNA expression level between PN and PPE (P>0.05) . However, PPAR-γ mRNA in the PPE group (0.33±0.14) was significantly lower than that in PN (0.52±0.16, P<0.01), and FABP-4 mRNA level in the PPE group (0.80±0.29) was significantly higher than in the PN group (0.63±0.22, P<0.01). (2) Western-blot showed the same tendency as the mRNA results. ①There were no statistical differences in the protein expression of PPAR-α, PPAR-ß, not in term groups (TN and TPE) , nor in premature groups (PN and PPE) . PPAR-γ protein level in the TPE group (0.46±0.17) was significantly lower than that in TN (0.65±0.20, P<0.01) and FABP-4 protein level in the TPE group (0.60±0.19) was significantly higher than that in the TN group (0.50±0.21, P<0.05). ②The PPAR-γ protein level in the PPE group (0.30±0.16) was significantly lower than that in the PN group (0.61±0.16, P<0.05), while the FABP-4 protein expression in the PPE group (0.58±0.19) was significantly higher than that in the PN group (0.40±0.19, P<0.05). (3) Linear correlation showed that: ①PPAR-γ protein expression correlated negatively with FABP-4 protein expresssion [P<0.01, R(2)=0.12 in the term groups (TN+TPE) , R(2)=0.15 in the premature groups (PN+PPE) ]. ②PPAR-γ protein expression correlated negatively with blood pressure recovery time, 24-hour urinary protein quantification and blood lipid recovery time (P<0.01, R(2)=0.37, 0.35, 0.18). FABP-4 protein expression correlated positively with lipid recovery time and blood cholesterol concentrations (P<0.01, R(2)=0.13, 0.25). Conclusions: The expression of PPAR-γ decreases in placentas from patients with pre-eclampsia, while the expression of FABP-4 increases. The expression of FABP-4 correlates negatively with the expression of PPAR-γ, and both are associated with the prognosis of pre-eclampsia.

Novel ultra-thin near-eye augmented-view device (UNAD).

The current augmented-view device for glaucoma patients are limited by the low angle minification (less than 3X), image overlapping and pupil mismatching. We present a novel ultra-thin near-eye augmented-view device (UNAD) with a proper minification angle of 4X to avoid scanning eye movements. The device is realized by one symmetrical ultra-thin off-axis eight-mirror reversed telescopic optical system (field-of-view (FOV): x:-34°~3°; y: -5°~-20°, 5°~20°) and one central un-minified optical system (FOV: -5°~5°), and hence, the system can achieve a FOV (x:-34°~3°; y: -20°~20°) without overlapping images. Furthermore, the device fully accounts for pupil matching with the entrance pupil of the human eye. Finally, the simulation results in CODE V and LightTools verify that our proposed system is feasible and has potential practical value for glaucoma patients.

Febuxostat-associated drug reaction with eosinophilia and systemic symptoms (DRESS).

WHAT IS KNOWN AND OBJECTIVE: Febuxostat is recommended as an alternative drug for gouty patients with a history of allopurinol hypersensitivity or carrying the HLA-B*5801 allele. CASE SUMMARY: An 81-year-old man with the medical history of gout presented to our clinic with generalized rashes for 2 days. After taking febuxostat for 2 days, he developed generalized skin rash with high fever. Laboratory tests showed elevated liver enzymes and acute kidney injury. WHAT IS KNOWN AND OBJECTIVE: This is the first identified case of febuxostat-associated DRESS. Febuxostat should be withdrawn immediately when DRESS is observed to avoid further serious complications.

Mutation analysis of PVRL1 in patients with non-syndromic cleft of the lip and/or palate in Guangdong.

Non-syndromic cleft of the lip and/or palate (NSCLP) is a very common birth defect; the poliovirus receptor-like 1 gene (PVRL1) has been identified as a genetic risk factor for NSCLP in patients from Norway, the Philippines, and South America. Given the considerable variation in allele frequencies across these geographical regions, this study explored the relationship between NSCLP and mutations of PVRL1 in patients from Guangdong, China. We recruited 171 NSCLP patients and 100 volunteers, and divided our samples into 2 groups: a sequencing group and a mass spectrometry group. In the sequencing group, we screened for mutations in exons 2 and 5 of PVRL1 by polymerase chain reaction and direct sequencing in 71 NSCLP patients and 100 volunteers. In the mass spectrometry group, we screened for amino acid mutations in α-spliced transcript codons 112, 131, and 395, and in the ß-spliced transcript codon 1082 using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis in 100 NSCLP patients and 100 volunteers. No mutations were detected in either PVRL1 exons 2 or 5 in the 71 NSCLP patients and 100 volunteers, nor did we find mutations of α-spliced transcript codons 112, 131, 395 and the ß-spliced transcript codon 1082 in any of the 100 NSCLP patients and 100 volunteers. Thus, mutations in exons 2 and 5 of PVRL1, and T334A, A391T, G1183A in the α-spliced transcript, and G1082T in the ß-spliced transcript do not participate in the development of NSCLP in patients from Guangdong.

Inhibition of melanogenesis by ß-caryophyllene from lime mint essential oil in mouse B16 melanoma cells.

OBJECTIVE: Volatile essential oils of mint species are used for cosmetics and in skin care products. In this study, we evaluated the main chemical components of the lime mint and the anti-melanogenic properties of its main components. METHODS: The essential oil was analysed by gas chromatography-mass spectrometry (GC/MS). The anti-melanogenic effects of mint essential oil and ß-caryophyllene were investigated in B16F10 murine melanoma cells. RESULTS: The main components of lime mint essential oil were found to be D-limonene (41.10%), D-carvone (8.58%), δ-selinene (6.73%) and ß-caryophyllene (6.24%). The lime mint essential oil reduced melanin production in a dose-dependent manner in murine B16F10 cells. ß-Caryophyllene, one of the main compounds in lime mint essential oil, could reduce melanogenesis by down-regulating the expression of MITF, TRP-1, TRP-2 and tyrosinase, resulting in a decrease in melanin content decrease. CONCLUSION: These results reveal that lime mint essential oil and ß-caryophyllene are considered to be valuable as potential skin-whitening agents.

Risk assessment of the outcome for cerebral infarction in tuberculous meningitis.

INTRODUCTION: Cerebral infarction in tuberculous meningitis is a major risk factor for permanent disability. This study assessed the clinical presentation of tuberculous meningitis and risks factors for cerebral infarction. OBSERVATION: Thirty-eight adult patients with tuberculous meningitis were studied between 2002 and 2006. Clinical, radiological, and laboratory data of patients with cerebral infarction were compared with those of patients without cerebral infarction. Patients with cerebral infarction were significantly older (65.1 vs 52.1years), had higher risk assessment scores (3.7 vs 2.2), and more often had basal meningeal enhancement on imaging (92.3% vs 60.0%), mild to moderate sequelae (69.2% vs 4%), an overall poor brain outcome (69.2% vs 8%), aspirin prescription (84% vs 8%), and neurosurgical intervention for hydrocephalus (54.0% vs 16.0%). Cerebral infarction patients were also more likely to have experienced doctor-related delays in antituberculosis (61.5% vs 36%) and corticosteroid (61.5% vs 32%) therapy. DISCUSSION AND CONCLUSION: The Framingham risk score would be an option for tuberculous meningitis patients to access cerebral infarction risk. Contrast-enhanced brain imaging is helpful for exploring basal meningeal enhancement, in order to obtain an early diagnosis. Antituberculosis, corticosteroid, and aspirin therapies should be started immediately when tuberculous meningitis is suspected.

Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits.

OBJECTIVE: Repairing articular cartilage is clinically challenging. We investigated a simple, effective and clinically feasible cell-based therapeutic approach using a poly(lactide-co-glycolide) (PLGA) scaffold seeded with autologous endothelial progenitor cells (EPC) to repair a full-thickness osteochondral defect in rabbits using a one-step surgery. METHODS: EPC obtained by purifying a small amount of peripheral blood from rabbits were seeded into a highly porous, biocompatible PLGA scaffold, namely, EPC-PLGA, and implanted into the osteochondral defect in the medial femoral condyle. Twenty two rabbits were randomized into one of three groups: the empty defect group (ED), the PLGA-only group or the EPC-PLGA group. The defect sites were evaluated 4 and 12 weeks after implantation. RESULTS: At the end of testing, only the EPC-PLGA group showed the development of new cartilage tissue with a smooth, transparent and integrated articular surface. Moreover, histological analysis showed obvious differences in cartilage regeneration. At week 4, the EPC-PLGA group showed considerably higher TGF-ß2 and TGF-ß3 expression, a greater amount of synthesized glycosaminoglycan (GAG) content, and a higher degree of osteochondral angiogenesis in repaired tissues. At week 12, the EPC-PLGA group showed enhanced hyaline cartilage regeneration with a normal columnar chondrocyte arrangement, higher SOX9 expression, and greater GAG and collagen type II (COLII) content. Moreover, the EPC-PLGA group showed organized osteochondral integration, the formation of vessel-rich tubercular bone and significantly higher bone volume per tissue volume and trabecular thickness (Tb.Th). CONCLUSION: The present EPC-PLGA cell delivery system generates a suitable in situ microenvironment for osteochondral regeneration without the supplement of exogenous growth factors.

Liquid chromatography-mass spectrometry method for the quantification of posaconazole in human plasma: application to pharmacokinetics following single-dose administration in the fasted state and with a high-fat meal.

A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed to determine concentrations of posaconazole in human plasma precipitated by acetonitrile including internal standard. Rapid chromatographic separation was achieved in the mobile phase composition of acetonitrile, water and formic acid (v/v/v, 55:45:0.1) with a flow rate of 0.25 ml/min. Posaconazole-d4 was used as internal standard. Detection was undertaken with cation electrospray tandem mass spectrometry on a Sciex/API3000. The method was accurate, specific and sensitive for the analysis of posaconazole in human plasma in the concentration range of 2-1000 ng/ml. The inter- and intra-batch accuracy was within +/- 10% and the lower limit of quantification was 2 ng/ml. The method facilitated a clinical pharmacokinetic study after oral administration of a single-dose of posaconazole suspension in the fasted state and with a high-fat meal in a two-period crossover design. Cmax (maximum concentration) and AUC (area under serum drug concentration) were significantly increased, and Tmax (time to maximum plasma concentration) was delayed under fed condition, which suggested that simultaneous administration of posaconazole with food may help to achieve higher plasma concentrations and result in better antifungal efficacy.

Thermomagnetic properties and its effects on Fisher entropy with Schioberg plus Manning-Rosen potential (SPMRP) using Nikiforov-Uvarov functional analysis (NUFA) and supersymmetric quantum mechanics (SUSYQM) methods.

Thermomagnetic properties, and its effects on Fisher information entropy with Schioberg plus Manning-Rosen potential are studied using NUFA and SUSYQM methods in the presence of the Greene-Aldrich approximation scheme to the centrifugal term. The wave function obtained was used to study Fisher information both in position and momentum spaces for different quantum states by the gamma function and digamma polynomials. The energy equation obtained in a closed form was used to deduce numerical energy spectra, partition function, and other thermomagnetic properties. The results show that with an application of AB and magnetic fields, the numerical energy eigenvalues for different magnetic quantum spins decrease as the quantum state increases and completely removes the degeneracy of the energy spectra. Also, the numerical computation of Fisher information satisfies Fisher information inequality products, indicating that the particles are more localized in the presence of external fields than in their absence, and the trend shows complete localization of quantum mechanical particles in all quantum states. Our potential reduces to Schioberg and Manning-Rosen potentials as special cases. Our potential reduces to Schioberg and Manning-Rosen potentials as special cases. The energy equations obtained from the NUFA and SUSYQM were the same, demonstrating a high level of mathematical precision.

α-Lipoic acid regulates lipid metabolism through induction of sirtuin 1 (SIRT1) and activation of AMP-activated protein kinase.

AIMS/HYPOTHESIS: Sirtuin 1 (SIRT1) is a longevity-associated protein, which regulates energy metabolism and lifespan in response to nutrient deprivation. It has been proposed to be a therapeutic target for obesity and metabolic syndrome. We investigated whether α-lipoic acid (ALA) exerts a lipid-lowering effect through regulation of SIRT1 activation and production in C(2)C(12) myotubes. METHODS: ALA-stimulated AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), adipose triacylglycerol lipase (ATGL) and fatty acid synthase (FAS) production, as well as intracellular triacylglycerol accumulation and fatty acid ß-oxidation were analysed in the absence or presence of a SIRT1 inhibitor (nicotinamide), SIRT1 small interfering (si) RNA and an AMPK inhibitor (compound C) in C(2)C(12) myotubes. Mice with streptozotocin/nicotinamide-induced diabetes and db/db mice fed on a high-fat diet were used to study the ALA-mediated lipid-lowering effects in vivo. RESULTS: ALA increased the NAD(+)/NADH ratio to enhance SIRT1 activity and production in C(2)C(12) myotubes. ALA subsequently increased AMPK and ACC phosphorylation, leading to increased palmitate ß-oxidation and decreased intracellular triacylglycerol accumulation in C(2)C(12) myotubes. In cells treated with nicotinamide or transfected with SIRT1 siRNA, ALA-mediated AMPK/ACC phosphorylation, intracellular triacylglycerol accumulation and palmitate ß-oxidation were reduced, suggesting that SIRT1 is an upstream regulator of AMPK. ALA increased ATGL and suppressed FAS protein production in C(2)C(12) myotubes. Oral administration of ALA in diabetic mice fed on a high-fat diet and db/db mice dramatically reduced the body weight and visceral fat content. CONCLUSIONS/INTERPRETATION: ALA activates both SIRT1 and AMPK, which leads to lipid-lowering effects in vitro and in vivo. These findings suggest that ALA may have beneficial effects in the treatment of dyslipidaemia and obesity.